Principles of hair cycle control.

The hair follicle (HF) undergoes life-long cyclic transformations between "resting" (telogen), growth (anagen), and apoptosis-driven regression (catagen). Contrary to conventional wisdom, cyclic remodelling affects even the distal HF epithelium; telogen is not a mere resting period, since it shows substantial metabolic and proliferative activity and may encompass a phase of controlled hair shaft-extrusion ("exogen"). Even under physiological circumstances, very few (malfunctioning?) HF may leave this cycle over time to be removed by inflammatory cells ("programmed organ deletion"). Although numerous systemic, metabolic, immunological, and nerve-derived factors (e.g. hormones, cytokines, neuropeptides, neurotransmitters, mast cells) can profoundly alter hair growth in vivo, neither vascular nor neural stimuli nor extrafollicular cells are essential for HF development or cycling. Rather, an intrafollicular "hair cycle clock" of as yet unknown nature drives the HF cycle. This elusive chronobiological timing device likely exploits secondary changes in the intra- and perifollicular signalling milieu for guiding the HF through its transformations. However, the supreme generator of cycling activity ("oscillator") that dictates any of these signalling switches is still as unknown as is its exact location. Since, clinically, the control of catagen is of paramount importance (too early anagen termination: alopecia, effluvium; catagen too late: hirsutism, hypertrichosis), the controls of catagen-associated keratinocyte apoptosis and of dermal papilla secretory activities are discussed as crucial targets for future therapeutic manipulations.